title: Systemic neutralizing antibodies induced by long interval mucosally primed systemically boosted immunization correlate with protection from mucosal SHIV challenge.
abstract: Immune correlates of vaccine protection from HIV-1 infection would provide important milestones to guide HIV-1 vaccine development. In a proof of concept study using mucosal priming and systemic boosting, the titer of neutralizing antibodies in sera was found to correlate with protection of mucosally exposed rhesus macaques from SHIV infection. Mucosal priming consisted of two sequential immunizations at 12-week intervals with replicating host range mutants of adenovirus type 5 (Ad5hr) expressing the HIV-1(89.6p) env gene. Following boosting with either heterologous recombinant protein or alphavirus replicons at 12-week intervals animals were intrarectally exposed to infectious doses of the CCR5 tropic SHIV(SF162p4). Heterologous mucosal prime systemic boost immunization elicited neutralizing antibodies (Nabs), antibody-dependent cytotoxicity (ADCC), and specific patterns of antibody binding to envelope peptides. Vaccine induced protection did not correlate with the type of boost nor T-cell responses, but rather with the Nab titer prior to exposure.
authors.affiliation: Department of Virology, Biomedical Primate Research Centre (BPRC), P.O. Box 3306, 2280 GH Rijswijk, The Netherlands. bogers@bprc.nl
authors.forename: Willy M J M
authors.initials: WM
authors.lastname: Bogers
authors.forename: David
authors.initials: D
authors.lastname: Davis
authors.forename: Ilona
authors.initials: I
authors.lastname: Baak
authors.forename: Elaine
authors.initials: E
authors.lastname: Kan
authors.forename: Sam
authors.initials: S
authors.lastname: Hofman
authors.forename: Yide
authors.initials: Y
authors.lastname: Sun
authors.forename: Daniella
authors.initials: D
authors.lastname: Mortier
authors.forename: Ying
authors.initials: Y
authors.lastname: Lian
authors.forename: Herman
authors.initials: H
authors.lastname: Oostermeijer
authors.forename: Zahra
authors.initials: Z
authors.lastname: Fagrouch
authors.forename: Rob
authors.initials: R
authors.lastname: Dubbes
authors.forename: Martin
authors.initials: M
authors.lastname: van der Maas
authors.forename: Petra
authors.initials: P
authors.lastname: Mooij
authors.forename: Gerrit
authors.initials: G
authors.lastname: Koopman
authors.forename: Ernst
authors.initials: E
authors.lastname: Verschoor
authors.forename: Johannes P M
authors.initials: JP
authors.lastname: Langedijk
authors.forename: Jun
authors.initials: J
authors.lastname: Zhao
authors.forename: Egidio
authors.initials: E
authors.lastname: Brocca-Cofano
authors.forename: Marjorie
authors.initials: M
authors.lastname: Robert-Guroff
authors.forename: Indresh
authors.initials: I
authors.lastname: Srivastava
authors.forename: Susan
authors.initials: S
authors.lastname: Barnett
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Heeney
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage*; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis*; D001483:Base Sequence; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D005260:Female; D015752:Genes, env; D015483:HIV Antibodies / Q000096:biosynthesis*; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D007111:Immunity, Cellular; D018928:Immunity, Mucosal; D007115:Immunization Schedule; D007117:Immunization, Secondary; D008253:Macaca mulatta; D008297:Male; D009500:Neutralization Tests; D018449:SAIDS Vaccines / Q000008:administration & dosage*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D014766:Viremia / Q000276:immunology / Q000517:prevention & control
chemical_list: D016915:AIDS Vaccines; D000914:Antibodies, Viral; D004279:DNA, Viral; D015483:HIV Antibodies; D018449:SAIDS Vaccines